This research program characterizes taste buds and their nerve supply in the vallate papilla of the mouse tongue. It further evaluates how this peripheral taste system is affected by altered genes for one or more neurotrophins. Gene function can be usefully examined by induced mutations in which a targeted gene is inactivated by homologous recombination or a transgene is inserted into a mouse line. In order to evaluate responsible neurotrophins, the tongue's developing taste system will be examined in induced mutant mice that have either a gain or a loss of neurotrophin function. The primary conceptual objective of this research is to evaluate whether the following biological principles apply to most taste neurons: I) Neurotrophins are required for the survival of developing sensory neurons. ii) Sensory neurons are required for the development of a variety of secondary receptor cells. This research program will specifically evaluate how taste neurons and taste buds are affected by inactivation of genes for one or more of the neurotrophins NT-3, NT-4 and BDNF or their cognate tyrosine kinase receptors. This research further proposes to examine transgenic animals carrying a neurotrophin transgene that increased epidermal neurotrophin levels which may thereby rescue neurotrophin-dependent neurons. These genetic models will clarify the role of neurotropohins in the sense of taste. Hence, by using induced mutant mice, this research will provide new approaches to evaluating chemosensory development. Research on neurotrophins and the rescue of neurotrophin-dependent neurons has promise in the assessment and treatment of neurodegeneratiave disorders such as Alzheimer's disease, ALS, and Parkinson's disease, as well as in familial dysautonomia, a genetic disorder in which taste buds fail to develop.